Sarcopenia is associated with poor prognosis in cancer pts and inflammation has been recognized as a hallmark of cancer. In this study, we investigated the synergistic effect of sarcopenia and inflammation on survival in advanced stage cancer pts treated with IO.
We performed a retrospective analysis of 90 pts treated on IO-based phase 1 clinical trials at Winship Cancer Institute of Emory University from 2009-2017. CT images at mid-L3 were obtained at baseline. Skeletal muscle density was obtained using SliceOmatic v5.0 by TomoVision and converted to skeletal muscle index (SMI) by dividing by height2. We defined sarcopenia as SMI<39. Neutrophil-to-lymphocyte ratio (NLR) was obtained at baseline and used as a surrogate of inflammation. Pts were categorized based on recursive partitioning methods into three groups: (1) low NLR, (2) high NLR without sarcopenia, (3) high NLR with sarcopenia. Overall survival (OS) and progression-free survival (PFS) were measured from date of first dose of IO to date of death or clinical or radiographic progression, respectively. Multivariable analysis (MVA) was carried out using Cox proportional hazard model.
The majority of pts (n = 53) were males and most (68.9%) had at least 2 prior lines of therapy. Melanoma (33%) and GI (22.2%) tumors were the most common histologies. Low NLR was associated with longer OS and PFS (Table). Sarcopenic pts with high NLR had shorter survival than pts with high NLR who were not sarcopenic (Table).Table: 133P
Univariable analysis (UVA) and MVA† of inflammation and sarcopenia with survival
|Median Survival in Months (95% CI)||N||HR (CI)||p-value||N||HR (CI)||p-value|
|Group 1: NLR <2.9||24.3 (10.3, 44.8)||36||--||--||36||--||--|
|Group 2: NLR ≥2.9, SMI ≥ 39||9.4 (5.5, NA)||33||2.65 (1.22-5.72)||0.013*||33||2.08 (0.90-4.77)||0.085|
|Group 3: NLR ≥ 2.9, SMI < 39||3.8 (2.8, 5.9)||21||8.40 (3.47-20.31)||<0.001*||21||7.93 (3.19-19.73)||<0.001*|
|Group 1: NLR <2.9||4 (2.5, 5.4)||36||--||--||34||--||--|
|Group 2: NLR ≥ 2.9, SMI ≥ 39||2.8 (1.6, 4.1)||33||1.62 (0.95-2.79)||0.078||33||1.35 (0.77-2.39)||0.298|
|Group 3: NLR ≥ 2.9, SMI < 39||1.6 (1.2, 1.8)||21||4.16 (2.26-7.67)||<0.001*||21||4.37 (2.26-8.48)||<0.001*|
†The multivariable model was built by controlling for gender, checkpoint indication, # of previous treatment lines, royal marsden hospital (RMH) risk group, age, ECOG PS, race, # of metastatic sites, and histology. *statistical significance at alpha < 0.05.
Sarcopenia may have a synergistic effect with inflammation on decreasing survival in pts treated with IO. Prospective validation of the impact of body composition parameters on survival and whether adipose tissue plays a role in the relationship may be warranted. Equal contribution: MAB, DJM, JMS.
Clinical trial identification
Legal entity responsible for the study
Emory University IRB.
Research reported in this publication was supported in part by the Biostatistics and Bioinformatics Shared Resource of the Winship Cancer Institute of Emory University and NIH/NCI under award number P30CA138292. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
M.A. Bilen: Consulting/advisory role: Exelixis, Sanofi; Research funding: Bayer, Bristol-Myers Squibb, Genentech/Roche, Incyte, Nektar, AstraZeneca, Tricon Pharmaceuticals, Peleton, Pfizer. B.C. Carthon: Consulting/advisory role: Astellas Medivation, Pfizer, Blue Earth Diagnostics; Travel accommodations: Bristol-Myers Squibb. W.L. Shaib: Research funding: ArQule and Lilly. R. Kudchadkar: Consulting/advisory role: Bristol-Myers Squibb, Novartis, Array BioPharma; Honorarium: Bristol-Myers Squibb; Research funding: Merck. B. El-Rayes: Consulting/advisory role: Merrimack, BTG, Bayer, Loxo, RTI Health Solutions; Speakers’ bureau: Lexicon, Bristol-Myers Squibb; Honorarium: Lexicon, RTI Health Solutions, and Bayer; Research funding: Taiho Pharmaceutical, Bristol-Myers Squibb, Boston Biomedical, Cleave Biosciences, Genentech, AVeo, Pfizer, Novartis, Hoosier Cancer Research Network, Five Prime Therapeutics, PPD Inc., Merck, ICON Clinical research. S.S. Ramalingam: Consulting/advisory role: Amgen, Boehringer Ingelheim, Celgene, Genetech/Roche, Lilly/ImClone, Bristol-Myers Squibb, AstraZeneca, Abbvie, Merck, and Takeda; Travel, accommodations: EMD Serono, Pfizer, and AstraZeneca. T.K. Owonikoko: Consulting/advisory role: Novartis, Celgene, Lilly, Sandoz, Abbvie, Eisai, G1 Therapeutics, Takeda, Seattle Genetics, Bristol-Myers Squibb, and MedImmune; Intellectual property of the following: “Overcoming acquired resistance to chemotherapy treatments through suppression of STAT3” and “Selective chemotherapy treatments and diagnostic methods related thereto”; Research funding: Novartis, Astellas Pharma, Celgene, Bayer, Stem CentRx, Regeneron, AstraZeneca/MedImmune, Abbvie, G1 Therapeutics, Bristol-Myers Squibb. All other authors have declared no conflicts of interest.